title: Systematic literature review and meta-analysis of the efficacy and safety of prescription opioids, including abuse-deterrent formulations, in non-cancer pain management.
abstract: OBJECTIVE
  This study was conducted to compare safety and efficacy outcomes between opioids formulated with technologies designed to deter or resist tampering (i.e., abuse-deterrent formulations [ADFs]) and non-ADFs for commonly prescribed opioids for treatment of non-cancer pain in adults.
  
  
  METHODS
  PubMed and Cochrane Library databases were searched for opioid publications between September 1, 2001 and August 31, 2011, and pivotal clinical trials from all years; abstracts from key pain conferences (2010-2011) were also reviewed. One hundred and ninety-one publications were initially identified, 68 of which met eligibility criteria and were systematically reviewed; a subset of 16 involved a placebo group (13 non-ADFs vs placebo, 3 ADFs vs placebo) and reported both efficacy and safety outcomes, and were included for a meta-analysis. Summary estimates of standardized difference in mean change of pain intensity (DMCPI), standardized difference in sum of pain intensity difference (DSPID), and odds ratios (ORs) of each adverse event (AE) were computed through random-effects estimates for ADFs (and non-ADFs) vs placebo. Indirect treatment comparisons were conducted to compare ADFs and non-ADFs.
  
  
  RESULTS
  Summary estimates for standardized DMCPI and for standardized DSPID indicated that ADFs and non-ADFs showed significantly greater efficacy than placebo in reducing pain intensity. Indirect analyses assessing the efficacy outcomes between ADFs and non-ADFs indicated that they were not significantly different (standardized DMCPI [0.39 {95% confidence interval (CI) 0.00-0.76}]; standardized DSPID [-0.22 {95% CI -0.74 to 0.30}]). ADFs and non-ADFs both were associated with higher odds of AEs than placebo. Odds ratios from indirect analyses comparing AEs for ADFs vs non-ADFs were not significant (nausea, 0.87 [0.24-3.12]; vomiting, 1.54 [0.40-5.97]; dizziness/vertigo, 0.61 [0.21-1.76]; headache, 1.42 [0.57-3.53]; somnolence/drowsiness, 0.47 [0.09-2.58]; constipation, 0.64 [0.28-1.49]; pruritus 0.41 [0.05-3.51]).
  
  
  CONCLUSIONS
  ADFs and non-ADFs had comparable efficacy and safety profiles, while both were more efficacious than placebo in reducing pain intensity.
authors.affiliation: Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Michna
authors.forename: Wendy Y
authors.initials: WY
authors.lastname: Cheng
authors.forename: Caroline
authors.initials: C
authors.lastname: Korves
authors.forename: Howard
authors.initials: H
authors.lastname: Birnbaum
authors.forename: Ryan
authors.initials: R
authors.lastname: Andrews
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ashish V
authors.initials: AV
authors.lastname: Joshi
authors.forename: David
authors.initials: D
authors.lastname: Schaaf
authors.forename: Jack
authors.initials: J
authors.lastname: Mardekian
authors.forename: Mei
authors.initials: M
authors.lastname: Sheng
mesh_terms: D000328:Adult; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic; D003248:Constipation / Q000139:chemically induced; D003692:Delayed-Action Preparations; D051271:Headache Disorders, Secondary / Q000209:etiology; D006801:Humans; D009294:Narcotics / Q000009:adverse effects* / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced; D009293:Opioid-Related Disorders / Q000517:prevention & control; D059408:Pain Management; D010149:Postoperative Pain / Q000188:drug therapy; D019966:Substance-Related Disorders / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D003692:Delayed-Action Preparations; D009294:Narcotics
keywords: Opioids; Pain Management; Safety